Impact of Metformin on the Severity and Outcomes of Acute Ischemic Stroke in Patients with Type 2 Diabetes Mellitus

Background: Diabetes mellitus (DM) is a major risk factor for cardiovascular disease. Metformin therapy reportedly decreases the risk of stroke, but the associations between metformin treatment and neurological severity or patient prognosis have not been investigated in clinical studies. This study evaluated the effects of metformin on stroke severity and outcomes in acute ischemic stroke patients with type 2 DM. Methods: We examined 355 stroke patients with type 2 DM without severe renal impairment or prestroke impairment of activities of daily living who were admitted to Kyushu Medical Center between April 2010 and September 2014. Neurological severity was assessed according to the National Institutes of Health Stroke Scale (NIHSS) score on admission. Mild neurological severity was defined as an NIHSS score lower than 3 on admission, and favorable functional outcome was defined as a modified Rankin Scale score of 2 or lower at discharge. Results: On logistic regression analysis with adjustments for multiple confounding factors, pretreatment with metformin was independently associated with mild neurological symptoms (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.09- 4.10; P=.026). In contrast, functional outcomes showed no significant associations. Nevertheless, a benefit of prior metformin use was observed in patients with a prior history of stroke (OR, 11.3; P=.046) and in patients after excluding those with mild stroke severity (OR, 5.64; P=.042). Conclusions: Administration of metformin in DM patients prior to stroke onset may be associated with reduced neurological severity and improved acute-phase therapy outcomes.